Subclasses of T lymphocytes, distinguished by the performance of different immune functions, can be categorized immunogenetically by the sets of Lyt components expressed on their surfaces. The generation of these subclasses involves divergent and sequential steps in differentiation governed by distinct gene programs. The same principles underlie the generation of B lymphocyte subclasses, although the immunogenetics of B lymphocyte diversification is not yet so far advanced. New Lyt and Lyb systems now under study will add further refinements. Now that we have some working knowledge of the genes and gene programs directing the development of these several cell populations, it is feasible to dissect disorders of immunocompetence in more precise terms. This grant proposal centers on absolute and relative enumeration of Lyt and Lyb subclasses in mice with genetic or experimental conditions affecting immunocompetence. First it is necessary to accumulate sufficient data on physiological changes in subclass variation with age, as a base-line for comparisons; for this we have chosen the C57BL/6 mouse, which has the advantage that we possess several Lyt and Lyb congenic stocks based on C57BL/6. Secondly we propose to examine mice carrying one of several relevant mutants, - df (Ames dwarf locus), dw (Snell-Bagg dwarf locus), Dh (dominant hemimelia), hr (hairless), and me (motheaten), - and mice of the SJL and CBA/N strains. Third we shall investigate the effects of neonatal splenectomy, and restitution of lethally-irradiated splenectomized mice, on Lyt and Lyb sub-population structure. The final aim is to relate all observed changes in Lyt and Lyb sub-population structure to discrete immunological functions.